T helper 1 (Th1) type cytokines and chemokines are bioactive mediators in inflammation underling several diseases and co-morbid conditions, such as cardiovascular and metabolic disorders. Th1 chemokine CXCL10 participates in heart damage initiation/progression; cardioprotection has been recently associated with sildenafil, a type 5 phosphodiesterase inhibitor. We aimed to evaluate the effect of sildenafil on CXCL10 in inflammatory conditions associated with diabetic cardiomyopathy. We analyzed: CXCL10 gene and protein in human cardiac, endothelial, and immune cells challenged by pro-inflammatory stimuli with and without sildenafil; serum CXCL10 in diabetic subjects at cardiomyopathy onset, before and after 3 months of treatment with sildenafil vs. placebo. Sildenafil significantly decreased CXCL10 protein secretion (IC50 = 2.6 x 10(-7)) and gene expression in human cardiomyocytes and significantly decreased circulating CXCL10 in subjects with chemokine basal level a parts per thousand yen 930 pg/ml, the cut-off value as assessed by ROC analysis. In conclusion, sildenafil could be a pharmacologic tool to control CXCL10-associated inflammation in diabetic cardiomyopathy.

Di Luigi, L., Corinaldesi, C., Colletti, M., Scolletta, S., Antinozzi, C., Vannelli, G.b., et al. (2016). Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy. INFLAMMATION, 39(3), 1238-1252 [10.1007/s10753-016-0359-6].

Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy

Poerio N.;Fraziano M.;
2016-01-01

Abstract

T helper 1 (Th1) type cytokines and chemokines are bioactive mediators in inflammation underling several diseases and co-morbid conditions, such as cardiovascular and metabolic disorders. Th1 chemokine CXCL10 participates in heart damage initiation/progression; cardioprotection has been recently associated with sildenafil, a type 5 phosphodiesterase inhibitor. We aimed to evaluate the effect of sildenafil on CXCL10 in inflammatory conditions associated with diabetic cardiomyopathy. We analyzed: CXCL10 gene and protein in human cardiac, endothelial, and immune cells challenged by pro-inflammatory stimuli with and without sildenafil; serum CXCL10 in diabetic subjects at cardiomyopathy onset, before and after 3 months of treatment with sildenafil vs. placebo. Sildenafil significantly decreased CXCL10 protein secretion (IC50 = 2.6 x 10(-7)) and gene expression in human cardiomyocytes and significantly decreased circulating CXCL10 in subjects with chemokine basal level a parts per thousand yen 930 pg/ml, the cut-off value as assessed by ROC analysis. In conclusion, sildenafil could be a pharmacologic tool to control CXCL10-associated inflammation in diabetic cardiomyopathy.
2016
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
Settore BIO/19 - MICROBIOLOGIA GENERALE
English
Con Impact Factor ISI
CXCL10; PDE5 inhibition; T helper 1; cardiomyopathy; inflammation; Cells, Cultured; Chemokine CXCL10; Diabetic Cardiomyopathies; Gene Expression; Humans; Inflammation; Myocytes, Cardiac; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
Di Luigi, L., Corinaldesi, C., Colletti, M., Scolletta, S., Antinozzi, C., Vannelli, G.b., et al. (2016). Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy. INFLAMMATION, 39(3), 1238-1252 [10.1007/s10753-016-0359-6].
Di Luigi, L; Corinaldesi, C; Colletti, M; Scolletta, S; Antinozzi, C; Vannelli, Gb; Giannetta, E; Gianfrilli, D; Isidori, Am; Migliaccio, S; Poerio, N; Fraziano, M; Lenzi, A; Crescioli, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/219344
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